Exercise effects on DNA methylation in EVL, CDKN2A (p14, ARF), and ESR1 in colon tissue from healthy men and women

ABSTRACT

Physical activity reduces risk of colon cancer by 20–30%. Aberrant methylation patterns are common epigenetic alterations in colorectal adenomas, and cancers and play a role in cancer initiation and progression. Alterations identified in normal colon tissue represent apotential ‘field cancerization’ process, where normal colon is primed for carcinogenesis. Here, we investigate methylation patterns in three genes –Ena/VASP-like (EVL), (CDKN2A (p14, ARF)), and Oestrogen Receptor-1 (ESR1)– in normal colon tissue collected at baseline and 12 months from 202 sedentary men and women, 40–75 years, enrolled in a randomized controlled trial testing an exercise intervention vs. control (http://clinicaltrials.gov/show/NCT00668161). Participants were randomized to moderate-to-vigorous intensity exercise, 60 minutes/day, 6 days/week for 12 months, or usual lifestyle. Sigmoid colon biopsies were obtained at baseline and 12-months, DNA extracted, and bisulphite converted. Droplet digital methylation-specific PCR was performed for EVL, p14ARF, and ESR1. Generalized estimating equations modification of linear regression was used to model relationships between intervention effects and gene methylation levels, adjusting for possible confounders.

There were no statistically significant differences between methylation patterns at 12-months between exercisers and controls. ESR1 methylation patterns differed by sex: women −10.58% (exercisers) +11.10% (controls); men +5.54% (exercisers), −8.16% (controls) (P=0.05), adjusting for BMI and age. There were no statistically significant changes in methylation patterns in any gene stratified by change in VO₂max or minutes/week of exercise.

While no statistically significant differences were found in gene methylation patterns comparing exercises vs. controls, 12-month exercise effects on ESR1 methylation differed by sex, warranting further study.

KEYWORDS:

• Methylation
• colon cancer
• droplet digital PCR
• exercise
• randomized controlled trial

Disclosure statement

The authors have no conflict of interest to report.

Additional information

Funding

This work was supported by the National Cancer Institute [R01 CA077572]; National Cancer Institute [R21 CA209203]; Breast CancerResearchFund [BCRF-19-107].